Cancer is an often fatal disease that affects a significant portion of the population. From 2000 to 2004 the National Cancer Institute estimated that the age-adjusted death rate due to cancer in the U.S. was 192.7 per 100,000 men and women per year. In January of 2003 approximately 10.5 million Americans had a history of cancer.
Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells. If the spread is not controlled, it can result in death. Cancer is caused by both external factors (tobacco, chemicals, radiation, and infectious organisms) and internal factors (inherited mutations, hormones, immune conditions, and mutations that occur from metabolism). The regulation of gene expression involved in cancer development has been heavily investigated, but therapeutics and methods for detecting cancer are still needed.
Cancer is considered a stem cell disease (Berns, A., Cell, 121:811-813 (2005)). Stem cells are characterized by self-renewal and further differentiation into multiple lineages (Bell, D. R., and Van Zant, G., Oncogene, 23:7290-7296 (2004)). Evidence suggests that the clonal nature of a tumor is derived from replenishment by a rare population of cancer-initiating cells, which acquire stem cell properties. Evidence also supports that the stromal region adjacent to a tumor mass may contain genetic changes within potential cancer stem cells. In contrast, the tumor mass may have DNA changes that are responsible for cancer progression but not for initiation. In addition, due to the circulating nature of blood, it is possible that chronic inflammation serves as a niche for circulating bone marrow stem or progenitor cells to mutate and develop. Thus, tumors from multiple tissues could be initiated from a similar stem cell origin, but differ only when they progress in a different environment at a later stage. Skin, lung and gastrointestinal tract are the three largest defensive surfaces of body (Berns, A., Cell, 121:811-813 (2005); Otto, W. R., J Pathol, 197:527-535 (2002)), and are underlined with enriched lymphatic tissues, which might contain stem cells derived from the circulation.
Transcriptional coactivator proteins coordinate gene expression in a large number of biological processes, including cancer development (McKenna N J, O'Malley B W, Cell, 108:465-474 (2002); Aranda A, Pascual A., Physiol Rev, 81:1269-1304 (2001)). Dysregulated coactivator functions, resulting from chromosomal aberrations in particular, have been suggested to promote oncogenesis (Yang, X. J., Nucleic Acids Res, 32:959-976 (2004); Greaves, M. F., Wiemels, J., Nat Rev Cancer, 3:639-649 (2003); Anzick, S. L., et al., Science 277:965-968 (1997)). Examples include coactivators CBP/p300 and TIF2, which are associated with chromosomal translocations in leukemia as fusion proteins (Yang, X. J., Nucleic Acids Res, 32:959-976 (2004)), and coactivators AIB1/SRC-3 and AIB3/TRBP, whose genes are amplified in breast cancers (Guan, X. Y., et al., Cancer Res, 56:3446-3450 (1996); Torres-Arzayus, M. I. et al., Cancer Cell 6:263-274 (2004)). Some oncoproteins have also been shown to have overlapping functions with coactivators (Brett, D., et al., Hum Mol Genet, 6:1559-1564 (1997)), implicating the involvement of transcriptional coactivator actions in cancer development.
Existing methods for detecting cancer and treating cancer typically lack specificity and are associated with adverse side effects.
Thus, it is an object of the invention to provide compositions and methods for the treatment of one or more symptoms associated with cancer.
It is another object of the invention to provide methods and compositions for the detection or diagnosis of cancer.
It is still another object to provide methods for screening for compounds that inhibit or alleviate one or more symptoms associated with pathologies due to cells having amplicons in CoAA.